Aminoglycoside antibiotics, for example, streptomycins, kanamycins, gentamicins, tobramycin etc. have practically been used as broad spectrum antimicrobials effective against gram-positive, gram-negative and acid-fast bacteria. The aminoglycoside antibiotics, however, are sometimes accompanied by undesired side effect such as nephropathy and deafness. Occurrence of resistant strains against the aminoglycosides is another problem to be solved. It has been attempted to modify such aminoglycosides with a specified acyl group at the 1-amino group in order to improve the antimicrobial activity and relatively decrease the side effect. For instance, amikacin, an excellent antimicrobial agent, which is prepared by acylation of the 1-amino group of kanamycin A with L-(-)-4-amino-2-hydroxybutyric acid, is effective against kanamycin A resistant strains and its toxicity is approximately the same as kanamycin A [described in J. Antibiotic, 25, 695 (1972) by Kawaguchi et al; U.S. Pat. No. 3,781,268 and J. Antibiotic, 27, 677 (1974) by Fujisawa et al].
The present inventors have found that the antimicrobial spectrum and the potency of activity are improved by acylation of the 1-amino group of aminoglycosides with .alpha.-hydroxy-.alpha.-heterocycleacetic acids. The present invention is based upon this finding.